ER-to-Golgi transport and SEC23-dependent COPII vesicles regulate T cell alloimmunity

Area of Science:

• Immunology
• Cell Biology
• Molecular Biology

Background:

• T cell effector functions rely on secreting molecules, but the regulation of this process is not fully understood.
• The endoplasmic reticulum (ER)-to-Golgi pathway is essential for protein transport and secretion.

Purpose of the Study:

• To investigate the role of the ER-to-Golgi pathway, specifically SEC23B, in T cell activation and protein secretion.
• To explore the functional redundancy between SEC23 paralogs in T cell immunity.

Main Methods:

• Generated mice with T cell-specific deletion of SEC23B (SEC23B-deficient T cells).
• Assessed T cell proliferation and effector functions in vitro and in vivo (allogeneic and xenogeneic transplantation models).
• Analyzed T cells from patients with congenital dyserythropoietic anemia II (CDAII) caused by SEC23B mutations.

Main Results:

• SEC23B deficiency in T cells impaired proliferation and effector functions.
• SEC23B-deficient T cells showed defects in vivo during transplantation models.
• T cells from CDAII patients, with compensatory SEC23A upregulation, did not show similar defects.
• Expression of SEC23A rescued T cell function in SEC23B-deficient mice.

Conclusions:

• SEC23B is critical for regulating the T cell secretome and effector functions.
• Functional overlap exists between SEC23A and SEC23B, highlighting paralog redundancy in T cell immunity.
• The COPII pathway plays a vital role in T cell-mediated immune responses.